We present an adolescent male with Noonan syndrome (NS) and celiac disease (CD) who attained normal adult height with growth hormone (GH) treatment and gluten-free diet (GFD).
A 15 ½ year old healthy male presented with short stature and delayed puberty. His mother and maternal grandmother were short with heights 142.2 cm and 147.3 cm, respectively. Examination showed bilateral epicanthal folds and down slanting eyes like his mother, fifth finger clinodactyly, height 147.5 cm (<1%; standard deviation score, −2.96), growth velocity 2.5 cm/y, weight 48.2 kg (11%; standard deviation score, −1.24), Tanner 2 pubic hair and Tanner 1 genitalia. Midparental target height was 169.1 cm. He had normal screening studies for GH deficiency and thyroid disorders, prepubertal gonadotropins and testosterone levels, and normal total immunoglobulin A, and elevated antitissue transglutaminase immunoglobulin A 134.7units/mL (0-20). Bone age was 13 years. Genetic evaluation revealed heterozygous missense variant of BRAF gene in him and his mother confirming a diagnosis of NS. He was diagnosed with CD by intestinal biopsy. Patient was started on GH therapy and a GFD with subsequent improvement in growth velocit (6.8-12.3 cm/y) and advancement of puberty. The patient stopped GH therapy at 17 ½ years with a height 165.9 cm.
Coexistence of NS caused by BRAF missense variant and CD has not been previously reported. Our patient attained normal adult height with GH therapy and GFD.
NS and CD can co-occur and addressing both these disorders can help patients attain normal height potential.
Non–islet cell tumor hypoglycemia (NICTH) is an uncommon condition, of which only a few cases caused by malignant phyllodes tumor of the breast have been reported. We describe a case of NICTH secondary to malignant phyllodes tumor with good response to glucocorticoid therapy.
A 62-year-old woman with a rapidly enlarging left breast mass presented with drowsiness and a capillary blood glucose level of 32.4 mg/dL. Her plasma glucose and insulin levels were 36.0 mg/dL (reference range, 72-144 mg/dL) and 0.6 mIU/L (reference range, 0.0-25.0 mIU/L), respectively. Her beta-hydroxybutyrate and c-peptide levels were undetectable. The insulin-like growth factor (IGF)-I and IGF-II levels were 37 μg/L (reference range, 43-220 μg/L) and 1062 ng/mL (reference range, 333-967 ng/mL), respectively, with an IGF-II:IGF-I molar ratio of 29.4. Prednisolone 30 mg per day was initiated with improvement in hypoglycemia. Outpatient flash glucose monitoring profile was stable with mild hypoglycemia (glucose level, 54-68.5 mg/dL) detected 5% of the time. The patient underwent left mastectomy with axillary clearance 4 weeks later. Histology was reported as malignant phyllodes tumor with extensive ductal carcinoma in situ. Prednisolone was stopped after surgery. The patient was treated with letrozole and adjuvant radiotherapy. There was no recurrence of hypoglycemia during the subsequent 24-month follow-up.
The mainstay of treatment for NICTH is surgical resection of the culprit tumor. Although glucocorticoid treatment has also been widely used for NICTH, few reports have demonstrated efficacy for NICTH secondary to phyllodes tumor.
We report a rare case of malignant phyllodes tumor of the breast resulting in NICTH and demonstrated good response to glucocorticoids as a bridge to definitive surgery.
Nonislet cell tumor hypoglycemia (NICTH) is an uncommon cause of hypoglycemia due to a relative surplus of insulin-like growth factor 2 (IGF-2) or its precursor molecule. The diagnosis is confirmed by an elevated ratio of IGF-2 to insulin-like growth factor 1 (IGF-1). Myoepithelial carcinoma (MECA) is a rare and aggressive salivary gland cancer that has not been previously associated with NICTH.
A 63-year-old female with a past medical history of metastatic salivary MECA, type 2 diabetes mellitus previously on metformin, hypertension, and hypothyroidism presented to her oncologist for chemotherapy and was found to have a serum glucose of 30 mg/dL (reference: 65-99). She was admitted for further diagnostic work-up which revealed an insulin level of <1 μU/mL (reference: 3-25), C-peptide <0.5 ng/mL (reference: 1.1-4.3), IGF-1 of 15 ng/mL (reference: 41-279), and IGF-2 of 147 ng/mL (reference: 180-580) with an IGF-2:IGF-1 molar ratio of 10, consistent with NICTH. The patient’s hypoglycemia unfortunately was quite resistant to treatment, requiring a combination of corticosteroids, continuous dextrose infusion, and somatostatin injections. The patient died 3 weeks after presenting with hypoglycemia.
Salivary MRCAs commonly contain pleomorphic adenoma gene 1 oncogene rearrangements which are associated with increased IGF-2 production and may predispose patients to hypoglycemia.
This case demonstrates that NICTH can be associated with metastatic salivary MECA. The hypoglycemia in this scenario is challenging to manage and is associated with poor prognosis.
Atypical femur fractures (AFFs) caused by long-term bisphosphonate use are associated with high rates of delayed healing and nonunion.
A 64-year-old woman with osteopenia on alendronate for 15 years sustained a displaced left AFF following a fall from standing height. Imaging showed an acute displaced transverse diaphyseal left femur fracture with lateral cortical thickening and beaking. She underwent an open reduction and internal fixation with insertion of a cephalomedullary nail placed in compression mode, utilizing a novel technique involving intraoperative removal of the endosteal hypertrophied cortical bone at the fracture site. Alendronate was stopped and teriparatide was initiated postoperatively. Radiographs at 3.5 months postsurgery showed evidence of normal fracture union with mature callus formation.
AFFs caused by prolonged bisphosphonate use have a high rate of delayed healing and nonunion due to abnormal bone remodeling. Use of teriparatide postoperatively has been shown to reduce healing time in small observational studies in surgically treated patients. Our case demonstrates an expedited healing time of 3.5 months using teriparatide combined with a novel surgical technique involving removal of a portion of the abnormally remodeled bone and placement of an intramedullary nail in compression mode.
Our case demonstrates an expedited healing time of 3.5 months compared to the average reported healing time for AFF of 10.7 months, supporting the use of the combination of teriparatide and a novel surgical technique.